5-APB

Last updated
5-APB
5-(2-aminopropyl)benzofuran.svg
5-APB molecule ball.png
Clinical data
Other names1-Benzofuran-5-ylpropan-2-amine
Routes of
administration 		Oral
Drug class Serotonin–norepinephrine–dopamine releasing agent; Serotonin 5-HT2 receptor agonist; Entactogen; Stimulant; Psychedelic
ATC code
  • None
Legal status
Legal status
  • AU: S9 (Prohibited substance)
  • BR: Class F2 (Prohibited psychotropics) [1]
  • DE: Anlage II (Authorized trade only, not prescriptible)
  • UK: Class B
  • UN:Unscheduled.
Identifiers
  • 1-(1-benzofuran-5-yl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C11H13NO
Molar mass 175.231 g·mol−1
3D model (JSmol)
  • CC(N)CC1=CC(C=CO2)=C2C=C1
  • InChI=1S/C11H13NO/c1-8(12)6-9-2-3-11-10(7-9)4-5-13-11/h2-5,7-8H,6,12H2,1H3 Yes check.svgY
  • Key:VKUMKUZDZWHMQU-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

5-APB, also known as 5-(2-aminopropyl)benzofuran, is an entactogen of the phenethylamine, amphetamine, and benzofuran families. 5-APB and related drugs have sometimes been informally called "Benzofury".

Contents

5-APB was first described in the scientific literature in 2000 [2] [3] [4] [5] and emerged as a novel designer drug in 2010. [3] [4] [6] [7]

Use and effects

Users describe the effects of 5-APB as including euphoria among others. [3] Largely, its effects reported were similar to those of the drug MDMA but not as strong.[ citation needed ] The drug has been reported to produce visual disturbances and is said to have mild psychedelic effects. [3] [8]

Recreational use of 5-APB has been associated with death in combination with other drugs [9] [10] and solely as the result of 5-APB. [11]

Interactions

Pharmacology

Pharmacodynamics

5-APB acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA), with EC50 Tooltip half-maximal effective concentration values for monoamine release of 19 nM for serotonin, 21 nM for norepinephrine, and 31 nM for dopamine in rat brain synaptosomes. [6] [12] It is also a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI). [6]

5-APB is a potent agonist of the serotonin 5-HT2A and 5-HT2B receptors. [6] [12] Its EC50 Tooltip half-maximal effective concentration (Emax Tooltip maximal efficacy) values were 6,300 nM (54%) at the serotonin 5-HT2A receptor and 280 nM (61–92%) at the serotonin 5-HT2B receptor. [6] [12] It also shows affinity for the serotonin 5-HT2C receptor (Ki = 880 nM) and the serotonin 5-HT1A receptor (Ki = 3,300 nM). [6] [12] It has been reported to act as an agonist of the serotonin 5-HT2C receptor similarly to the serotonin 5-HT2A and 5-HT2B receptors. [3] [13] The drug's potent agonism of the serotonin 5-HT2B receptor makes it likely that 5-APB would be cardiotoxic with long-term use, as seen with other serotonin 5-HT2B receptor agonists such as fenfluramine and MDMA.[ citation needed ]

5-APB also shows high affinity for the mouse and rat trace amine-associated receptor 1 (TAAR1). [6]

In animal studies, 5-APB produces robust hyperlocomotion, robust conditioned place preference (CPP) but limited self-administration, fully substitutes for MDMA in drug discrimination tests, and partially substitutes for DOM, cocaine, and methamphetamine in drug discrimination tests. [14]

Chemistry

5-APB, also known as 5-(2-aminopropyl)benzofuran, is a phenethylamine, amphetamine, and benzofuran and an analogue of 3,4-methylenedioxyamphetamine (MDA).

Properties

5-APB is commonly found as the succinate and hydrochloride salt. The hydrochloride salt is 10% more potent by mass and doses should be adjusted accordingly.

Synthesis

The chemical synthesis of 5-APB has been described. [5]

Detection

A forensic standard of 5-APB is available, and the compound has been posted on the Forendex website of potential drugs of abuse. [15] The US Department of Justice and DEA have also conducted studies concerning the detection of 5-APB. [16]

Analogues

Analogues of 5-APB include MDA, 5-APDB, 5-MAPB, 6-APB, 5-APBT, and 5-API, among others.

History

5-APB, along with 6-APB, was first described in the scientific literature by Karin Briner and colleagues at Eli Lilly and Company in a patent in 2000. [2] [3] [4] [5] They were specifically studied as serotonin 5-HT2C receptor agonists for potential medical applications at this time. [2] [3] [4] [5] The description of 5-APB and 6-APB in the literature had followed the earlier work on 5-APDB and 6-APDB as serotonin releasing agents and entactogens by David E. Nichols and colleagues at Purdue University in 1993. [4] [6] [17] 5-APB, along with 6-APB, emerged as a novel designer drug in 2010. [3] [4] [6] [7] 5-APB and 6-APB are often confused with 5-APDB and 6-APDB. [4]

Society and culture

United Kingdom

On March 5, 2014 the UK Home Office announced that 5-APB would be made a class B drug on 10 June 2014 alongside every other benzofuran entactogen and many structurally related drugs. [18]

See also

References

  1. ↑ Anvisa (2023-07-24). "RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-07-25). Archived from the original on 2023-08-27. Retrieved 2023-08-27.
  2. 1 2 3 Brandt SD, Walters HM, Partilla JS, Blough BE, Kavanagh PV, Baumann MH (December 2020). "The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats". Psychopharmacology (Berl). 237 (12): 3703–3714. doi:10.1007/s00213-020-05648-z. PMC   7686291 . PMID   32875347. The synthetic preparation of both 5-APB and 6-APB was first published in 2000 as part of a research program designed for the development of selective 5-HT2C receptor agonists (Briner et al. 2000; Briner et al. 2006), and the preparation of other isomers was reported for forensic purposes a decade later (Casale and Hays 2012; Stanczuk et al. 2013).
  3. 1 2 3 4 5 6 7 8 Greene, Shaun L (2013). "Benzofurans and Benzodifurans". Novel Psychoactive Substances. Elsevier. pp. 383–392. doi:10.1016/b978-0-12-415816-0.00016-x. ISBN   978-0-12-415816-0 . Retrieved 15 April 2025. A patent granted to Eli Lilly and Company in 2006 classifies 5-APB and 6-APB as 5HT2C receptor agonists [15]. [...] Internet user reports of 5-APB and 6-APB date from late 2010 [13]. [...] [15] Briner K, Burkhart JP, Burkholder TM, et al. Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists. 7045545 (US patent). Published 2000-01-19, issued 2006-16-03.
  4. 1 2 3 4 5 6 7 Roque Bravo R, Carmo H, Carvalho F, Bastos ML, Dias da Silva D (August 2019). "Benzo fury: A new trend in the drug misuse scene". J Appl Toxicol. 39 (8): 1083–1095. doi:10.1002/jat.3774. PMID   30723925. The first benzofurans appearing on the drug scene in 2010‐11, were 5‐(2‐aminopropyl) benzofuran (5‐APB) and 6‐(2‐aminopropyl) benzofuran (6‐APB). These compounds had been previously patented in 2006 as potential therapeutic drugs for eating disorders and seizures, due to their action as serotonergic agonists (Advisory Council on the Misuse of Drugs, 2013; Taschwer, Hofer, & Schmid, 2014). While these first two molecules are the subject of most published investigations, namely those concerning pharmacological aspects, other benzofuran analogues have also been marketed as "legal highs." Examples of such analogues are 5‐(2‐ aminopropyl)‐2,3‐dihydrobenzofuran (5‐APDB) and 6‐(2‐aminopropyl)‐ 2,3‐dihydrobenzofuran (6‐APDB), first synthesized in 1993, purportedly as non‐neurotoxic benzofuran analogues of 3,4‐methylenedioxyamphetamine (MDA) (Monte, Marona‐Lewicka, Cozzi, & Nichols, 1993). These drugs are often confused with 5‐APB and 6‐APB (Casale, 2012; Casale & Hays, 2011).
  5. 1 2 3 4 USpatent 7045545,Briner K, Burkhart JP, Burkholder TP, Fisher MJ, Gritton WH, Kohlman DT, Liang SX, Miller SC, Mullaney JT, Xu YC, Xu Y,"Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists",published 19 January 2000,issued 16 May 2006, assigned to Eli Lilly Co.
  6. 1 2 3 4 5 6 7 8 9 Rickli A, Kopf S, Hoener MC, Liechti ME (July 2015). "Pharmacological profile of novel psychoactive benzofurans". British Journal of Pharmacology. 172 (13): 3412–3425. doi:10.1111/bph.13128. PMC   4500375 . PMID   25765500. [5-APB] and [6-APB] are benzofuran analogues of MDA (Figure 1). [5-APDB] and [6-APDB] are dihydrobenzofuran analogues (Figure 1) that were originally synthesized for research purposes (Monte et al., 1993). [...] 5-APB and 6-APB appeared on the drug market in 2010– 2011 (Chan et al., 2013; Jebadurai et al., 2013; Stanczuk et al., 2013; Archer et al., 2014; Elliott and Evans, 2014; King, 2014), with reports of intoxication (Chan et al., 2013; Greene, 2013; Jebadurai et al., 2013; Seetohul and Pounder, 2013).
  7. 1 2 http://www.emcdda.europa.eu/publications/implementation-reports/2010 EMCDDA–Europol 2010 Annual Report on the implementation of Council Decision 2005/387/JHA
  8. ↑ Canal, Clinton E. (2018). "Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action". New Psychoactive Substances. Handbook of Experimental Pharmacology. Vol. 252. Cham: Springer International Publishing. pp. 227–260. doi: 10.1007/164_2018_107 . ISBN   978-3-030-10560-0. PMC   6136989 . PMID   29532180. Despite micromolar 5-HT1A affinities (Rickli et al. 2015b), Nbenzylphenethylamines retain potent psychedelic effects. Also, benzofurans, such as 5-APB and 6-APB, are potent and efficacious 5-HT2B agonists but have very low potency at 5-HT2A receptors. They also stimulate efflux of DA and 5-HT and have activity at TAAR1 receptors (Iversen et al. 2013; Rickli et al. 2015a), but anecdotal reports note that psychedelic effects are relatively minor compared to classic psychedelics. These observations provide further credence that the 5-HT2A receptor, but not 5-HT1A, 5-HT2B, TAAR1, or monoamine transporters, initiates psychedelic effects.
  9. ↑ "UCSD student dies of drug overdose after on-campus music festival". Los Angeles Times . August 20, 2014.
  10. ↑ Dawson P, Opacka-Juffry J, Moffatt JD, Daniju Y, Dutta N, Ramsey J, Davidson C (January 2014). "The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent vasoconstriction in the rat" (PDF). Progress in Neuro-Psychopharmacology & Biological Psychiatry. 48: 57–63. doi:10.1016/j.pnpbp.2013.08.013. PMID   24012617. S2CID   23400101. 5-APB ... has been implicated in 10 recent drug-related deaths in the UK
  11. ↑ McIntyre IM, Gary RD, Trochta A, Stolberg S, Stabley R (March 2015). "Acute 5-(2-aminopropyl)benzofuran (5-APB) intoxication and fatality: a case report with postmortem concentrations". Journal of Analytical Toxicology. 39 (2): 156–9. doi: 10.1093/jat/bku131 . PMID   25429871.
  12. 1 2 3 4 Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (January 2013). "Neurochemical profiles of some novel psychoactive substances". European Journal of Pharmacology. 700 (1–3): 147–151. doi:10.1016/j.ejphar.2012.12.006. PMC   3582025 . PMID   23261499.
  13. ↑ USpatent 7045545,Karin Briner et al,"Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists",published 2000-01-19,issued 2006-16-03
  14. ↑ Dolan SB, Forster MJ, Gatch MB (November 2017). "Discriminative stimulus and locomotor effects of para-substituted and benzofuran analogs of amphetamine". Drug Alcohol Depend. 180: 39–45. doi:10.1016/j.drugalcdep.2017.07.041. PMC   6463889 . PMID   28865391.
  15. ↑ Southern Association of Forensic Scientists, http://forendex.southernforensic.org/index.php/detail/index/1135 Archived 2014-05-29 at the Wayback Machine
  16. ↑ USDOJ/DEA, http://www.justice.gov/dea/pr/microgram-journals/2011/mj8-2_62-74.pdf
  17. ↑ Luethi D, Liechti ME (April 2020). "Designer drugs: mechanism of action and adverse effects". Arch Toxicol. 94 (4): 1085–1133. doi:10.1007/s00204-020-02693-7. PMC   7225206 . PMID   32249347. Some benzofuran designer drugs were originally investigated as part of a study that examined the role of ring oxygen atoms in interactions between MDA and monoamine transporters (Monte et al. 1993). [...] Monte AP, Marona-Lewicka D, Cozzi NV, Nichols DE (1993) Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogues of 3,4-(methylenedioxy)amphetamine. J Med Chem 36(23):3700–3706. https://doi.org/10. 1021/jm00075a027{{cite journal}}: External link in |quote= (help)
  18. ↑ UK Home Office (2014-03-05). "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014". UK Government. Retrieved 2014-03-11.
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